Proliferation of the vascular endothelium is one of the early and critical steps of angiogenesis encouraging cellular growth. The aim of this research proposal is to define the roles of the positive angiogenic factor, called the vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) in the cellular and molecular sequence of events by which estrogens produce tumor angiogenesis in the rat pituitary. Four specific aims are outlined to attain this objective over a period of three years. Specific aim 1 will elucidate the impact of estrogens on the expression of VEGF164 and NRP-1 in the pituitaries of different strains of rats and their F1 hybrid progenies by analyzing the genes and protein products. In specific aim 2 the mechanisms involved in the interaction between estrogen and VEGF164 and NRP-1 at the transcriptional level will be examined. The third aimwill elucidate the role of NRP-1, over expressed in prolactin secreting pituitary tumor cells, on cell survival and angiogenesis. Specific aim 4will address the question whether negative regulators like thrombospondin-1 that influence the action of VEGF164 during the development of estrogen induced tumor angiogenesis control the expression of NRP-1.